Angiotensin-II (A-II) plays an essential role in blood pressure regulation via effects on arteriorlar smooth muscle contraction and aldosterone synthesis in the adrenal zona glomerulosa. The mechanism of action of A-II is poorly understood, and it is unclear whether Ca++ or cyclic nucleotides function as the intracellualr "2nd messenger". Presumably, A-II sitmulates steroidogenesis by a mechanism similar to that of ACTH. Recently, we have obtained evidence indicating that ACTH controls steroidognesis via rapid and dramatic effects on phospholipids of the phosphatidate-polyphosphoinositide cycle. Specifically, de novo synthesis of phosphatidic acid is rapidly stimulated by ACTH, presumably via increased substrate availability, and this leads to rapid increases in CDP-diacylglycerol, phosphatidylglycerol-phosphate, phosphatidylglycerol, phosphatidylinosi-tol, diphosphoinositide, and triphosphoinositide. Those phospholipids having more than one phosphate in their polar head group directly stimulate mitochondrial cholesterol side-chain cleavage, and may therefore serve as ultimate effectors in steroidogenesis. In ACTH action, cAMP produces similar effects on this phospholipid pathway, and a liable protein, long known to be required for steroidogenesis, is required for the de novo synthesis of phosphatidic acid. Ca++ is required in cAMP action on phospholipid metabolism, and, indeed, Ca++ may be the ulitmate regulator for increasing substrate flow for phosphatidate synthesis. In a preliminary study, we have recently reported that relatively high concentrations of A-II elicit changes in adrenal capsular phospholipid metabolism which are similar to those provoked by ACTH, but different from those reported for A-II in the liver. The presently proposed research will attempt to define more fully the effects of A-II on phospholipid metabolism, and determine the role of phospholipid metabolism in A-II action in its target tissues. We will evaluate the effects of Ca++ and cAMP on phospholipid metabolism, and this should provide insight into the question of which "2nd messenger" is operative in A-II action. We will also test the hypothesis that phospholipids may function as "post-2nd messenger" mediators in A-II action.